Optical photothermal IR (OPTIR) microscopy for chemical imaging of living cells at sub-micron resolution Project Summary/Abstract Photothermal Spectroscopy Corp (PSC) and Prof. Ji-Xin Cheng of Boston University in collaboration with Prof. Rohith Reddy (University of Houston) propose to develop, validate, and commercialize a novel technical called Optical Photothermal Infrared (OPTIR) spectroscopy. This optical microscope-based instrument that will provide microscopic chemical analysis and chemical imaging for the life sciences with sub-micron spatial resolution. The new OPTIR technique is based on infrared (IR) spectroscopy, one on the most commonly used analytical techniques for chemical analysis. IR spectroscopy has already been applied to diverse research problems in the biomedical sciences, but it has not been widely applied for live cell research because of two key limitations. First, fundamental limits on spatial resolution (~3 ? 30 m) have prevented broad application of IR microscopy to single-cell and sub-cellular investigations. Second, strong IR absorption by water has dramatically hindered application of IR spectroscopy to live cells and other hydrated samples. Leveraging successful Phase I research, this proposal aims to overcome the key barriers of conventional IR spectroscopy, while also providing ~10X better spatial resolution. This project will involve two major thrusts: (1) the development of a commercial OPTIR microscope that is designed specifically for the life sciences research community; (2) demonstration and validation of the OPTIR technology on specific problems in cancer research. Commercial instrument development will be performed at PSC facilities in Santa Barbara CA in collaboration with the group of Prof. Ji-Xin Cheng at Boston University. The cancer related research will be performed at both Boston University and the University of Houston. Instrument development activities will include the development of a fully engineering OTPIR prototype for the life sciences community, focus on improvements in spatial resolution, measurement speed, ease of use, and compatibility with measurements of live cells and other hydrated samples in physiological environments. Cancer related research will focus on using the OPTIR technique to measure and map key spectroscopic markers that are indicators of cancerous cells and cancer aggressiveness. Further studies will investigate correlations between IR spectroscopic markers and tumor fighting efficacy. The project team is uniquely qualified to perform this work. PI Prof. Cheng is an award-winning research pioneer in development and application of novel spectroscopic and imaging techniques for the life sciences while the technical and commercial team at PSC has decades of successful experience developing and commercializing high resolution imaging and analytical instrumentation. Project collaborator Prof. Reddy is an award winning researcher with extensive expertise in the application of infrared spectroscopy to issues in cancer research. Successful completion of this project will lead to a next-generation single-cell analysis tool that will profoundly impact cellular and sub-cellular biology by providing functional information about changes in cellular state, including membrane order, protein folding, and DNA damage. These changes can be measured in live cells and over time to provide new insights into processes in health and disease.